摘要
目的探讨子宫颈鳞状细胞癌发生、发展过程中基因变化的规律。方法选择46例伴有高级别不典型增生的子宫颈鳞状上皮细胞癌,采用显微切割、聚合酶链反应、聚丙烯酰胺高压电泳、放射自显影等技术,对照分析正常组织、上皮内瘤样变(CIN)(Ⅱ,Ⅲ级)、子宫颈鳞状上皮细胞癌中9号染色体上7个微卫星位点的等位基因杂合性丢失(LOH)的变化。结果CIN(Ⅱ,Ⅲ级)总LOH率为16%,子宫颈鳞状上皮细胞癌总LOH率为25%。7个微卫星位点的LOH在前者依次为D9S171(30%),D9S162(23%),D9S43(20%),D9S303(17%),D9S753(12%),D9S242(11%),而在D9S1748上未发现有LOH的发生;后者依次为D9S171(41%),D9S43(33%),D9S162(31%),D9S242(24%),D9S303(17%),D9S753(17%),D9S1748(13%)。有CIN(Ⅱ,Ⅲ级)3例患者(第16例在D9S303、第42例在D9S171、第34例在D9S162位点)出现LOH,而在子宫颈鳞状细胞癌中未发生。结论从正常鳞状上皮至CIN再到浸润性子宫颈鳞状细胞癌,有基因异常累积的发生;p15基因的失活与子宫颈癌的发生高度相关;在D9S43,D9S162及D9S242上或其附近可能也存在与子宫颈癌发生相关的抑癌基因;有的高级别不典型增生与子宫颈鳞状上皮细胞癌源自不同克隆,从基因水平为子宫颈癌的多灶性发生提供了理论依据。
Objective To investigate the regulation of gene variation and explore the tumor associated suppressor genes on chromosome 9 during the developing of cervical squamous cell carcinoma. Methods Microdissection, PCR, electrophoresis and radiograph were selected to detect the LOH in 46 cases cervical squamous cell carcinoma with high-grade squamous dysplasia and normal tissue. The changes of LOH at chromosome 9 total seven microsatellite markers and relationship between LOH rate and clinical parameters were analysed. Results Total frequency of LOH in CIN （Ⅱ,Ⅲ） was 16 % and in cervical squamous cell carcinoma was 25 %. In the former, LOH at marker D9S171（30 %）, D9S162（23 %）, D9S43（20 %）, D9S303 （17 %）, D9S753（12 %）, D9S242（11%） were found, whereas D9S1748 LOH was not detected in high-grade dysplasia. In the latter, LOH at marker D9S171（41%）, D9S43（33 %）, D9S162（31%）, D9S242（24 %）, D9S303 （17 %）, D9S753（17 %）, D9S1748 13 % were found. In addition, LOH was found in high-grade dysplasia in three cases but not in cervical squamous cell carcinoma. Conclusions The study in seven microsatellite markers showed that from normal squamous tissue to dysplasia to cervical squamous cell carcinoma were accompanied with accumulation of gene errors. The pl 5 gene inactivation had a high relationship with the occur of cervical squamous cell carcinoma. Tumor suppressor genes associated with cervical squamous cell carcinoma may exist near or at D9S43, D9S162, D9S242. Some cases showed that high-grade dysplasia and cervical squamous cell carcinoma may came from different independent clone which provide some clue for multiple foci carcinoma at genetic level.
出处
《肿瘤研究与临床》
CAS
2006年第12期795-798,共4页
Cancer Research and Clinic
基金
山西省自然科学基金资助项目(20051112)
关键词
子宫颈鳞状细胞癌
基因丢失
Loss of genes
Cercival squamous cell carcinoma
